Biomedical HIV prevention tools including oral pre-exposure prophylaxis (PrEP) and vaginal microbicidal rings hold unique value for high-risk women who may have limited capacity for condom negotiation, including the key populations of sex workers and drug users. Commercial sex is a PrEP indicator in CDC guidelines, yet little is known about female sex workers' (FSWs) knowledge of and attitudes toward PrEP or the recently developed monthly vaginal microbicide rings. We describe knowledge and attitudes toward PrEP and microbicide rings in a sample of 60 mostly drug-using FSWs in Baltimore, Maryland, a high HIV-prevalence US city. Just 33% had heard of PrEP, but 65% were interested in taking daily oral PrEP and 76% were interested in a microbicide vaginal ring; 87% were interested in at least one of the two methods. Results suggest method mix will be important as biomedical tools for HIV prophylaxis are implemented and scaled up in this population, as 12% were interested in PrEP but not vaginal rings, while 19% were interested in vaginal rings but not in PrEP. Self-efficacy for daily oral adherence was high (79%) and 78% were interested in using PrEP even if condoms were still necessary. Women who had experienced recent client-perpetrated violence were significantly more interested in PrEP (86% vs 53%, p = 0.009) and microbicidal rings (91% vs 65%, p = 0.028) than women who had not recently experienced violence. No differences were observed by demographics nor HIV risk behaviors, suggesting broad potential interest in daily PrEP and monthly-use vaginal microbicides in this high-risk population.